{"doi":"10.1016/j.conb.2021.09.003","title":"Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2","abstract":null,"journal":"Current Opinion in Neurobiology","year":2022,"id":608133,"datarank":0.6190701577567639,"base_score":4.127134385045092,"endowment":4.127134385045092,"self_citation_contribution":0.6190701577567639,"citation_network_contribution":0.0,"self_endowment_contribution":0.6190701577567639,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1196232,"name":"Sarah K. Tschirner","orcid":"0009-0007-4972-9811","position":1,"is_corresponding":false},{"id":934167,"name":"Harald Steiner","orcid":"0000-0003-3935-0318","position":2,"is_corresponding":false},{"id":64859,"name":"Stefan Frieder Lichtenthaler","orcid":"0000-0003-2211-2575","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2.","abstract":"Secretases are a group of proteases that are major drug targets considered for the prevention and treatment of Alzheimer's disease (AD). Secretases do not only process the AD-linked neuronal amyloid precursor protein (APP) but also the triggering receptor expressed on myeloid cells 2 (TREM2), thereby controlling microglial functions. This review highlights selected recent discoveries for the α-secretases a disintegrin and metalloprotease 10 (ADAM10) and a disintegrin and metalloprotease 17 (ADAM17), the β-secretase β-site APP cleaving enzyme 1 (BACE1) and γ-secretase and their link to AD. New genetic evidence strengthens the role of α-secretases in AD through cleavage of APP and TREM2. Novel proteins were linked to AD, which control α- and β-secretase activity through transcriptional and post-translational mechanisms. Finally, new opportunities but also challenges are discussed for pharmacologically targeting β- and γ-secretase cleavage of APP and α-secretase cleavage of TREM2 with the aim to prevent or treat AD.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34689040","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"EU Joint Programme – Neurodegenerative Disease Research","grant_id":"01ED2002B","title":null},{"funder_name":"EU Joint Programme – Neurodegenerative Disease Research","grant_id":"FKZ161L0214C","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"263531414/FOR2290","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Bundesministerium für Bildung und Forschung","grant_id":"","title":null}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"Elsevier TDM","oa_locations":[{"url":"https://epub.ub.uni-muenchen.de/115385/1/115385.pdf","host_type":"repository"},{"url":"https://doi.org/10.1016/j.conb.2021.09.003","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/34689040","host_type":""},{"url":"https://dx.doi.org/10.1016/j.conb.2021.09.003","host_type":""},{"url":"https://pub.dzne.de/record/163268","host_type":""},{"url":"https://epub.ub.uni-muenchen.de/115385/","host_type":""}],"fields_of_study":["0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Humans","Alzheimer Disease","Amyloid beta-Protein Precursor","Membrane Glycoproteins","Receptors, Immunologic","Amyloid Precursor Protein Secretases","Aspartic Acid Endopeptidases","Amyloid beta-Peptides","Proteolysis","ADAM10 Protein"],"keywords":["Membrane Glycoproteins: therapeutic use","ADAM10 Protein: metabolism","Amyloid beta-Protein Precursor: metabolism","Amyloid Precursor Protein Secretases: therapeutic use","ADAM10 Protein","Amyloid beta-Protein Precursor","Alzheimer Disease","Aspartic Acid Endopeptidases","Humans","Receptors, Immunologic","Amyloid beta-Protein Precursor: therapeutic use","Aspartic Acid Endopeptidases: therapeutic use","Receptors, Immunologic: therapeutic use","info:eu-repo/classification/ddc/610","Amyloid beta-Protein Precursor: genetics","Amyloid beta-Peptides","Membrane Glycoproteins","Aspartic Acid Endopeptidases: genetics","Aspartic Acid Endopeptidases: metabolism","Receptors, Immunologic: metabolism","Amyloid beta-Peptides: therapeutic use","Amyloid Precursor Protein Secretases: metabolism","Amyloid beta-Peptides: metabolism","Membrane Glycoproteins: metabolism","Amyloid Precursor Protein Secretases: genetics","Proteolysis","Amyloid Precursor Protein Secretases","ADAM10 Protein: therapeutic use"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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